The effects of maternal diabetes on perinatal development patterns and hormonal regulation of enzymes concerned with adaptation to extra-uterine life are under study. Offspring of streptozotocin induced diabetic rats serve as the animal model. In livers of term fetal offspring of diabetic mothers (ODM), total and active forms of glycogen synthase activity are substantially elevated above normal and total and active forms of glycogen phosphorylase activity are slightly reduced. In lung of ODM, however, the active form of glycogen synthase activity is depressed. These alterations in the active forms of these glycogen metabolizing enzyme levels may be responsible for the observed increased accumulation of glycogen in livers and decreased glycogen level in lungs of term fetal ODM. Investigation of effects of maternal diabetes on rate limiting glycolytic enzymes indicated that phosphofructokinase and pyruvate kinase were elevated and hexokinase remained unchaged in liver, whereas all three enzyme activities were reduced in the lung of term fetal ODM. Preliminary evidence suggests that ODM manifest transient elevations above normal in neonatal development of two hepatic gluconeogenic enzymes, phosphoenolpyruvate carboxykinase and glucose-6-phosphatase, immediately following vaginal delivery. The induction of these two enzymes by glucagon, demonstrable in normal neonates, is curtailed in neonatal ODM. These findings suggest that maternal diabetes elicits alterations in: the fetal development of glycogen metabolizing and several glycolytic enzymes of liver and lung; the neonatal development of two hepatic gluconeogenic enzymes; and the hormonal inducibility of the latter.